THE  STRUCTURE  OF  DISALICYL  ALDEHYDE  AND  THE 
FORMATION  OF  DIOXANS 

BY 

CLARENCE  WILLIAM  KREGER 
A.  B.  Miami  University  1919 


THESIS 

Submitted  in  Partial  Fulfillment  of  the  Requirements  for  the 

Degree  of 

MASTER  OF  ARTS 
IN  CHEMISTRY 

IN 

THE  GRADUATE  SCHOOL 

OF  THE 

UNIVERSITY  OF  ILLINOIS 
1922 


K ^ 

UNIVERSITY  OF  ILLINOIS 

THE  GRADUATE  SCHOOL 

January  16  1 92  3_ 

I HEREBY  RECOMMEND  THAT  THE  THESIS  PREPARED  UNDER  MY 

supervision  by Clarence  W.  Kreger 

ENTITLED  The  Structure  of  Disalicyl  Aldehyde  and 

The  Formation  of  Dioxans. 

BE  ACCEPTED  AS  FULFILLING  THIS  PART  OF  THE  REQUIREMENTS  FOR 
THE  degree  OF  Master  of  Arts  in  Chemistry 


Recommendation  concurred  in* 

Committee 

on 

Final  Examination* 


^Required  for  doctor’s  degree  but  not  for  master’s 


_ 1 


Digitized  by  the  Internet  Archive 
in  2016 


https://archive.org/details/structureofdisalOOkreg 


ACKNOWLEDGMENT 


I wish  to  extend  my  sincere  thanks 
and  appreciation  to  Professor  Roger  Adams 
for  the  suggestion  of  this  problem,  and 
for  the  interest  he  has  shown  and  the  help 
ful  suggestions  which  he  has  given  during 
the  experimental  work. 


' 


the  structure  of  disalicyl  aldehyde 

AND 

THE  FORMATION  OF  DIOXANS. 


TABLE  OF  CONTENTS. 

Page 

I. 

INTRODUCTION 

1 

II. 

HISTORICAL  PART 

3 

III. 

THEORETICAL  PART 

6 

(l)  Disalicyl  Aldehyde 

6 

(3)  Aliphatic  Bis-Dioxans 

10 

(3)  The  1,3  Dioxans 

13 

IV. 

EXPERIMENTAL  PART 

18 

Preparation  of: 

(l)  Disalicyl  aldehyde 

18 

(2)  Salicyl  aldehyde  triacetate 

19 

(3)  5, 6-benzo-2 -phenyl -1 ,3-dioxan 

30 

(4)  Benzyl idene  diacetate 

21 

(5)  5, 6-benzo-3-p-chlorophenyl-l ,3-dioxan 

33 

(6)  5, 6-benzo-2-p-bromophenyl-l ,3-dioxan 

33 

(7)  5,6-benzo-3-m-nitrophenyl-l ,3-dioxan 

35 

(8)  Saligenin 

36 

(9)  Nitro-saligenin 

37 

(10)  Bromomethyl  alcohol 

38 

V. 

. SUMMARY 

30 

VI. 

BIBLIOGRAPHY 

33 

- 1 - 

PART  I 

INTRODUCTION 


One  of  the  very  common  derivatives  of  salicyl  aldehyde, 
and  one  which  is  very  easily  formed  is  the  so-called  disalicyl 
aldehyde.  This  compound  has  been  known  since  the  year  1845  and 
many  chemists  have  worked  with  it  since  that  time.  Despite  these 
facts  no  satisfactory  formula  has  as  yet  been  suggested  for  it. 

The  work  described  in  this  paper  was  taken  up  with  the  idea 
of  definitely  proving  that  disalicyl  aldehyde  has  the  following 
formula: 


It  was  proposed  to  show  that  this  formula  accounts  for  all 
the  known  properties  of  the  substance*  that  a possible  mechan- 
ism for  the  formation  of  such  a structure  from  salicyl  aldehyde 
can  be  devised  and  that  from  this  mechanism  conclusions  can  be 
drawn  as  to  new  methods  by  which  it  should  be  possible  to  prepare 
disalicyl  aldehyde  from  salicyl  aldehyde:  that  from  the  mechan* 

ism  of  the  formation  of  disalicyl  aldehyde,  conclusions  can  be 
drawn  as  to  the  formation  of  a compound  from  saligenin  and  ben- 
zaldehyde  which  should  possess  similar  properties  to  disalicyl 
aldehyde :and  that  the  reaction  of  the  formation  of  this  compound 
from  saligenin  and  benzaldehyde  is  not  limited  to  these  two 
substances,  but  is  a general  reaction,  yielding  similar  compounds 
with  substituted  benzaldehydes  and  substituted  saligenins. 


- 

. 

. 

. . . 


; . *Z  . 


: 

_ : 

- j *:  - • 

: 

■ 

l . • • - 


- 3 - 

It  should  be  mentioned  here  that  in  the  inaugural  dissertation 

of  Walter  P.  Bradley  for  the  degree  of  Doctor  of  Philosophy  at 

Goettingen  in  1890,  the  formula  given  above  was  mentioned  as  a 

possibility  for  the  structure, of  disalicyl  aldehyde.  No  proof 

was  given  by  Bradley,  however,  that  this  structure  was  correct, 

(i) 

and  in  publishing  an  abstract  of  his  thesis,  he  did  not  even 
mention  this  formula. 


. 


: 


. 


, ■ 


* 


- 3 - 
PART  II 

HISTORICAL  PART 


(3) 

As  early  as  1845,  disalioyl  aldehyde  was  found  along  with 

salicyl  aldehyde  when  the  copper  salt  of  salicyl  aldehyde  7/as 

(3) 

distilled.  In  1851,  Cahours  obtained  this  same  product  by  the 

action  of  benzoyl  chloride  upon  salicyl  aldehyde  while  attempting 

( 4) 

to  prepare  the  benzoyl  derivative.  Perkin,  a little  later, 
showed  that  acetyl  chloride  or  euccinyl  chloride  on  salicyl  alde- 
hyde yielded  the  same  product.  Since  that  time,  it  has  been 

shown  that  practically  all  types  of  acid  chloride  cause  this 

(5) 

same  reaction  to  take  place;  thus  phosphorus  trichloride, 

(6)  (?) 

urea  chloride,  phosgene  in  pyridine,  and  oxalyl  chloride  in 

(8) 

pyridine.  Investigations  have. indicated  that  the  product  is 

readily  prepared  by  the  action  of  acetyl  chloride  upon  salicyl 

aldehyde  in  glacial  acetic  acid  as  a solvent:  moreover,  many  of 

the  substituted  salicyl  aldehydes  yield  substituted  disalioyl 

(9) 

aldehydes  by  the  same  treatment. 

The  history  of  the  dioxans  does  not  date  back  so  far.  Only 
a few  are  known  and  these  are  of  rather  recent  origin.  The 
dioxans  are  six  membered  ring  bodies  with  two  oxygen  atoms  and 
four  carbon  atoms  in  the  ring.  The  possible  formulae  for  these 
rings  are:- 


i 


- 4 - 


There  are  no  known  examples  of  compounds  having  a nucleus 

structure  of  type  I.  Several  examples  of  compounds  having  a 

nucleus  structure  of  types  II  and  III  are  known.  Those  of  type  II 

are  of  particular  interest  in  this  paper  because  the  dioxans 

prepared  by  the  author  are  of  this  type.  These  are  1,3  dioxans, 

(10), 

according  to  the  nomenclature  given  in  Meyer  and  Jacobson, 

the  numbering  of  the  ring  being  as  shown  above. 

The  simplest  known  compound  of  thia  type  is  the  methylene 

ether  of  trimethylene  glycol  or  1,3  dioxan.  It  was  prepared  by 

(11) 

Henry,  in  1903, and  has  the  following  structural  formula:- 

C Hz 


C H* 


The  methylene  ether  of  saligenin  is  also  a 1,3  dioxan,  and 

this  compound  is  known  as  the  hitro  derivative.  It  was  first 

(13) 

prepared  by  Borsche  and  Berkhout.  It  is  made  by  the  action 
of  formaldehyde  on  p-nitrophenol  in  the  presence  of  dilute  sul- 
furic acid.  It  is  5 nitro  saligenin  methylene  ether  or  5,6-p- 
nitrobenzo-1 ,3-dioxan. 


>c  Hz. 


Compounds  containing  two  1,3  dioxan  nuclei  are  also  known. 


. .. 


- 


. . 


- . 


* 

i 

• 

- . . • 


J 


. 


. 


• • - 


- 5 - 


These  are  of  the  general  type: 


O — CH*  c 

/ 3 H-  \ / * 3 \ 

Tj-fiO  * Cd'  rCH-Tf 

\ ’ / \ U ! / 

® — C//  £//*  — O 


(13) 

and  were  prepared  by  Read,  by  the  action  of  aldehydes  (RCHD) 
on  pentaerythritol  (C(CHsOH)4) 


6 


PART  III 

THEORETICAL  PART 


Disalicyi  Aldehyde. 

The  empirical  formula  and  properties  of  disalicyi  aldehyde 

have  been  determined  in  part  by  many  of  the  investigators  who 

(14) 

obtained  this  product.  It  has  the  formula  C1^H1o03,  correspond- 
ing to  two  molecules  of  salicyl  aldehyde  with  a molecule  of  water 
eliminated.  It  gives  no  reaction  for  an  aldehyde  or  ketone  group 
with  such  reagents  as  phenyl  hydrazine,  hydroxyl amine  or  sodium 
bisulfite.  It  gives  no  reaction  for  a hydroxyl  group  with  such 
reagents  as  ferric  chloride,  acetyl  chloride  or  acetic  anhydride, 
and  is  insoluble  in  sodium  hydroxide  solution.  Disalicyi  aldehyde 
is  extraordinarily  stable  to  alkali,  being  undecomposed  after  long 
boiling  with  a concentrated  potassium  hydroxide  solution  or  even 
fusion  with  potassium  hydroxide.  On  the  other  hand,  concentrated 
sulfuric  acid  dissolves  it  upon  warming  to  give  a red  solution 
which  upon  careful  dilution  yields  salicyl  aldehyde.  Bromine  gives 
a mixture  of  bromo-salicyl  aldehyde  and  dibromodisalicyl  aldehyde. 
Strong  nitric  aoid  decomposes  it  and  yields  a certain  amount  of 
dinitrosalicylic  acid. 

In  an  attempt  to  write  structural  formulas  which  would  account 
for  the  properties  of  the  disalicyi  aldehyde,  two  have  been  found, 
(1)  and  (2) : 


6) 


n- 


(?) 


y\ 


— OH  — O - 

— o — C H- 


- 


. 


. 


■ 

. 


' ' 


■ 


7 


These  structures  contain  no  hydroxyl  or  carbonyl  groups:  more- 

over, being  acetals,  they  would  be  expected  to  be  stable  to 
alkalis  and  unstable  to  acids.  Formula  (l)  would  seem  unlikely 
on  account  of  the  four  merabered  rings  which  are  ordinarily  diffi- 
cult to  form  and  rare.  It  was,  therefore,  eliminated  and  the 
investigation  started  to  determine  whether  formula  (2)  was  the 
correct  structure  for  disalicyl  aldehyde. 

A possible  mechanism  by  which  such  a substance  could  be 
produced  from  salicyl  aldehyde  is  as  follows: 


V 


- G- 


O — 


\ 


0(H 


\ 


X- 


- h*Q 

— > 


CH  - G — 

\ 

o 


— CH- 


It  may  be  seen  that  the  first  step  involves  the  formation  of  an 
acetal  between  the  hydroxyl  of  one  molecule  of  salicyl  aldehyde 
and  the  aldehyde  group  of  the  second  molecule.  This  reaction 
corresponds  to  that  which  takes  place  when  phenols  or  naphthols 
react  with  benzaldehyde.  Phenols  or  naphthols  do  not  react  with 
benzaldehyde  unless  a mineral  acid  is  used  and  then  the  reaction 


• 

•« 

. 

• 

. 

- 8 - 

goes  readily  with  or  without  a solvent  such  as  glacial  acetic 

(15) 

acid.  Ordinarily,  triphenyl  methane  derivatives  are  obtained 
(16) 

but  Claisen  has  shown  that  by  working  at  low  temperatures, 
the  acetals  from  certain  of  the  phenols  and  naphthols  could  be 
isolated  as  intermediate  products.  Whereas  ordinary  phenol  benz- 
aldehyde  acetals  tend  chiefly  to  rearrange  to  triphenyl  methane 
compounds,  this  salicyl  aldehyde  hemiacetal  of  salicyl  aldehyde 
has  a tendency  to  condense  as  shown  in  steps  (3)  and  (3),  which 
involve  respectively  acetal  formation  and  dehydration  to  form 
di salicyl  aldehyde. 

If  this  explanation  is  correct,  it  may  be  understood  why 
various  acid  chlorides  cause  the  reaction  to  take  place.  A small 
amount  of  acid  chloride  reacts  first  with  the  hydroxyl  of  the 
salicyl  aldehyde,  giving  hydrochloric  acid.  This  mineral  acid 
being  the  catalyst  usually  used  for  the  formation  of  an  acetal 
causes  steps  (1)  and  (3)  to  occur.  The  remaining  portion  of  the 
acid  chloride  now  acts  as  a dehydrating  agent  to  remove  water 
and  thus  gives  step  (3).  This  deduction  leads  to  the  conclusion 
that  any  very  small  amount  of  mineral  acid  in  the  presence  of  a 
dehydrating  agent  should  cause  this  reaction  to  take  place.  Exper 
iments  fully  substantiated  this.  Salicyl  aldehyde  is  unaffected 
by  cold  acetic  anhydride  even  after  long  standing.  If  to  this 
mixture,  however,  a small  drop  of  concentrated  sulfuric  acid  is 
added,  an  immediate  reaction  takes  place.  The  mixture  turns  red 
and  heat  is  evolved  sufficient  to  boil  the  acetic  anhydride  if  it 


' 

- 

- 9 - 

is  not  cooled.  Inside  of  three  minutes  after  the  sudden  reaction 
is  over  disalicyl  aldehyde  separates  from  the  cooled  reaction 
mixture  in  yields  which  amount  to  over  80^>  of  the  theory.  In 
place  of  sulfuric  acid,  phosphoric  acid  or  hydrochloric  acid  may 
used. 

Acids  are  catalyzers  for  the  decomposition  as  well  as  for  the 
formation  of  acetals.  Treatment  of  disalicyl  aldehyde  with  con- 
centrated sulfuric  acid  to  yield  salicyl  aldehyde  has  already 
been  mentioned.  Warming  with  strong  aoid  is  rather  drastic  treat- 
ment , however.  A very  simple  experiment  showing  the  decomposition 
of  disalicyl  aldehyde  with  acids  consists  in  treating  pure  di- 
salicyl aldehyde  with  an  excess  of  acetic  anhydride.  No  reaction 
takes  plaoe,  even  on  long  boiling;  if,  however,  a drop  of  sulfur- 
ic acid  is  added  to  the  cold  solution  and  the  mixture  allowed  to 
remain  at  room  temperature,  large, heavy,  transparent  crystals 
separate  from  the  solution  within  twenty-four  hours.  These 
crystals  are  salicyl  aldehyde  triacetate. 

-f-  3 (CH^C °)z  O 

Och(ococHo)2 

sCHs  C -l 

OCOCHs 

The  structure  represented  by  disalicyl  aldehyde  involves  a new 
type  of  nucleus  and  consequently  it  is  necessary  to  outline 


- 10 


a convenient  system  of  nomenclature.  The  following  formula  repre 
sents  the  nucleus  and  numbered  as  in  the  figure  should  be  called 
a 1,3,7  bis-dioxan: 


I 


By  using  this  system  of  nomenclature,  disalicyl  aldehyde  is  then 
4,5-8 , 9-dibenzo-l , 3 , 7-bi3-dioxan. 

Aliphatic  Bis-Di oxana 

The  formation  of  a bis-dioxan  from  salicyl  aldehyde  is  of 
more  than  ordinary  interest  because  of  the  fact  that  salicyl  aide 
hyde  should  resemble  in  its  reactions  aliphatic  ^-hydroxy-alde- 
hydes. These  latter  substances  should,  therefore,  be  expected  to 
form  bis-dioxans.  It  is  a well-known  fact  that  aldol,  which  is 
a representative  of  the  class  of  ^3  -hydroxy-aldehydes,  enters 
into  a vigorous  reaction  on  the  addition  of  a small  amount  of 
sulfuric  acid,  giving  off  maeh  much  heat  and  thus  resembling  the 
action  of  acid  on  salicyl  aldehyde.  A certain  amount  of  croton 
aldehyde  forms,  but  in  addition,  a large  amount  of  by-product, 
the  nature  of  which  is  being  studied. 

Aldol  ( /3-oxy-butyraldehyde)  is  prepared  by  treating  acet- 

, , (!■?), 

aldehyde  with  dilute  hydrochloric  acid  (Wurtz  ).  If  this 
mixture  is  allowed  to  stand  for  some  time,  water  separates,  and 


- 11 


the  so-called  "Dialdan"  is  obtained.  This  is  a crystalline  body 
melting  at  139°-140°,  and  has  the  empirical  formula  C8H1403. 

This  corresponds  to  two  molecules  of  aldol  with  a molecule  of 
water  eliminated. 

~H30 

3(CH3CH(0H)CH2-CH0)  - ■■  > C8H1403 

* (IS) 

In  an  earlier  paper,  Wurtz  states  that  this  compound  is  the 
anhydride  of  aldol:  (C4H70)  ^0. 

„ (19) 

In  a later  paper  Wurtz  changes  his  opinion  and  assigns  the 
following  structure  to  dialdan :- 

CH  - CH(OH)  - CH2  -CHO 

ll 

CH  - CHa  - CH(OH)  - CHS 

tl 

Despite  the  fact  that  Wurtz  offers  several  reasons  for 
assigning  this  structure  to  this  so-called  dialdan,  its  structural 
formula  is  always  written  with  a question  mark  following  it,  and 
it  has  never  been  proven  definitely  just  what  the  structure  is. 

Since  aldol  resembles  salicyl  aldehyde  in  its  action  toward 
acid,  and  since  it  is  a representative  of  the  -hydroxy-alde- 

hydes which  should  resemble  salicyl  aldehydes  in  their  reactions: 
it  is  logical  to  believe  that  this  dialdan  is  none  other  than 
the  bis-dioxan  of  aldol.  If  the  reaction  of  two  molecules  of 
aldol  losing  one  molecule  of  water  is  explained  in  the  same  manner 
as  was  the  formation  of  di salicyl  aldehyde  from  salicyl  aldehyde, 
we  get  the  following  mechanism: 


' 


. 


. ... 


. ... 


I - • 


* 

, l • 

* 

' 

. 


. 

. 

. 


HzC 


h-c~oh 

C Hz 

1 

+ I 

GHz 

1 

Lc 

ho-g-  h 

1 

C H3 

- 13  - 


C Ha 

I 

H —C— OH 

GHz 

1/ 

H-C“ 


O 


o 


gHz 


c-  H 

I 

C H 3 


This  gives  a 1 ,3,7-bis-dioxan  very  similar  to  disalioyl 
aldehyde  and  using  the  same  nomenclature  as  was  used  in  naming 
the  nucleus  of  disalioyl  aldehyde  - the  so-called  dial  dan  be- 
comes 4, 8-dime thyl-1 ,3,7-bis-dioxan.  The  empirical  formula  for 
the  bis-dioxan  is  C8H1403  - corresponding  exactly  to  that  given 

rf 

by  Wurtz  for  dial dan. 

Experimental  work  is  now  under  way  to  prove  that  the  compound 
which  Wurtz  called  dial  dan  is  really  a bis-dioxan  corresponding 
to  disalioyl  aldehyde  in  structure.  The  proposed  procedure  is 
to  treat  aldol  in  identically  the  same  manner  as  salicyl  alde- 
hyde was  treated  in  the  formation  of  disalioyl  aldehyde. (This 
paper,  experimental  part).  This  should  give  a compound  whose 
physical  properties  are  similar  to  those  of  dial  dan;  but  whose 


: 


- 13 


chemcial  properties  correspond  to  those  of  a bis-dioxan  and  which 
will  lead  to  definite  proof  of  the  fact  that  the  so-called  di- 
al dan  is  really  4,8-dimethyl*5! ,3,7-bis-dioxan. 


The  1,3-Dioxans 

If  the  steps  (3)  and  (3)  described  in  the  mechanism  for  the 
formation  of  disalicyl  aldehyde  are  correct,  it  should  be  possible 
to  form  with  ease  a compound  of  similar  properties  to  disalicyl 
aldehyde  by  the  condensation  of  salignnin  with  benzaldehyde.  The 
analogy  is  best  shown  by  the  two  following  equations: 


It  is  true  that  the  hydroxyl  group  in  the  saligenin  is  an  alcohol 
while  that  in  the  intermediate  step  of  the  formation  of  disalicyl 
aldehyde  is  a hemiacetal  hydroxyl,  nevertheless  the  reactions 
should  proceed  in  somewhat  a similar  manner.  The  experiments 
came  up  to  expectations.  The  reaction  between  saligenin  and  ben- 
zaldehyde does  take  place  with  the  greatest  ease  and  doss  give  a 

compound  which  is  exactly  analogous  to  disalicyl  aldehyde  in 

it 

properties.  In  fact,  the  reaction  goes  so  readily  that/is  merely 
necessary  to  warm  together  these  two  substanoes  in  the  presence 
of  a very  small  amount  of  acid  without  the  use  of  a solvent  or 


* 


* 

. • 

■ 


. ... 


■ • “ ' 

; 


* i <. 

.1  . Li  • ■ • 


. 

. • ' * t 

> : - 


- 14  - 


dehydrating  agent.  To  get  the  best  results  in  forming  disalicyl 
aldehyde,  a high  temperature  must  be  avoided:  likewise  a high 

temperature  must  be  avoided  in  the  formation  of  this  new  product. 
The  compound  forms  with  such  ease  that  even  benzoic  acid  acts  as 
a catalyser  and  in  fact  it  is  preferable  to  use  this  rather  than 
hydrochloric  acid,  since  the  latter  tends  to  cause  saligenin  to 
condense  with  itself  to  a certain  extent,  thus  lowering  the  yield 
of  desired  product. 

This  new  condensation  product  of  saligenin  and  benzaldehyde 
is  5,6  benzo-3-phenyl-l,3-dioxan  or  phenyl  methylene  saligenin. 
Both  names  are  derived  from  nomenclatures  given  in  Meyer  and 
Jacobson.  The  dioxan  nomenclature  is  probably  the  best  because 
it  gives  a distinct  idea  of  the  structure  of  the  compound. 


/ . 


The  5, 6-benzo-2-phenyl-l ,3-dioxan  is  a well  crystallized 
compound,  unreacted  upon  by  hydroxyl  or  carbonyl  group  reagents, 
insoluble  in  and  extremely  stable  to  alkalis.  It  dissolves  in 
warm  concentrated  sulfuric  acid  to  a red  solution,  which  on 
dilution  gives  benzaldehyde  and  a resinous  substance,  presumably 
a saligenin  condensation  product.  These  properties  are  exactly 
similar  to  those  of  disalioyl  aldehyde,  and  the  compound  decomposes 


. 


; 


. ^ 


. 

. 

- 15 


in  a similar  manner  to  disalicyl  aldehyde  when  dissolved  in 
acetic  anhydride  and  treated  with  a drop  of  sulfuric  acid.  Ben- 
zylidine  diacetate  is  readily  obtained,  together  with  a saligenin 


The  ease  with  which  the  condensation  of  saligenin  and 
benzaldehyde  took  place  led  to  the  conclusion  that  other  alde- 
hydes should  react  in  the  same  way  with  saligenin  to  give  similar 
products.  Experiments  quickly  verified  this  conclusion. 

Para-chlorobenzaldehyde  and  para-bromo -benzaldehyde  condense 
very  readily  with  saligenin  to  give  the  corresponding  dioxans: 


These  are  respectively  5, 6-benzo-3-p-chloro-phenyl-l ,3-dioxan 
or  p-chlorophenyl  methylene  saligenin,  and  5, 6-benzo-3-p-bromo- 
phenyl-1 ,3-dioxan  or  p-brcmophenyl  methylene  saligenin.  The 
condensations  to  form  these  dioxans  take  place  so  readily  that 
it  is  merely  necessary  to  warm  the  mixture  of  saligenin  and  one 
of  the  above  aldehydes  until  a uniform  melt  is  obtained.  On 


7*esi  n 


- 16 


standing  at  room  temperature,  the  entire  mass  solidifies  into  a 
quantitative  yield  of  the  dioxan.  The  halogens  in  the  aldehyde 
molecule  activate  the  aldehyde  to  such  an  extent  that  the  reaction 
goes  without  the  use  of  a cond.ensing  agent  such  as  benzoic  acid 
or  hydrochloric  acid.  If  the  reaction  mixture  is  heated  longer 
than  is  necessary  to  obtain  a uniform  melt,  resinificaticn  of  the 
saligenin  takes  place  and  the  yields  of  the  dioxan  are  correspond- 
ingly lower.  The  condensation  of  saligenin  with  the  halogen 
substituted  benzaldehydes  can  also  be  carried  out  in  benzene  as 
a solvent.  Long  heating  is  necessary,  however,  and  the  yields 
are  not  so  good. 

These  dioxans  crystallize  in  beautiful  colorless  needles  of 
varying  length  up  to  one  half  inch.  Their  properties  are  exactly 
similar  to  those  of  5,6-benzo-2-phenyl-l,3-dioxan  and  of  disalicyl 
aldehyde. 

Saligenin  also  condenses  with  m-nitrobenzaldehyde  to  give 
the  corresponding  dioxan.  This  condensation  does  not  take  place 
so  readily  and  benzoic  acid  must  be  used  as  a condensing  agent. 

The  yields  are  not  very  good  and  the  product  could  not  be  obtained 
in  any  definite  crystalline  form.  This  condensation  product  is 
5,6-benzo-2-m-nitrophenyl-l ,3-dioxan  or  m-nitrophenyl  methylene 
saligenin:  ^ 


t 


. 

- 

• 

. 

. 

... 


. 


...  • \'j. 

. , ' 


■ 

...  . . 


V 


. 


< ' • . - : • • ' • • 


. 


- 17 


and  it  possesses  properties  exactly  similar  to  those  of  the  other 
dioxans  prepared. 

A striking  example  showing  the  similarity  of  these  dioxans 

and  their  preparation  to  that  of  disalicyl  aldehyde  was  brought 

out  when  an  attempt  was  made  to  condense  nitro-saligenin  with 

benzaldehyde.  The  nitro-saligenin  was  prepared  by  the  method 

(30) 

suggested  by  Hart  and  Hirschf elder , and  every  known  means  to 

condense  it  with  benzaldehyde  were  tried  without  success.  In 

their  work  on  the  preparation  of  disalicyl  aldehyde  from  substi- 

(9) 

tuted  salicyl  aldehydes,  Bradley  and  Dains  found  that  nitro- 
salicyl  aldehyde  prevented  the  condensation  to  the  corresponding 
disalicyl  aldehyde  from  taking  place.  These  authors  found  that 
the  introduction  of  negative  groups  hinders  or  entirely  prevents 
the  formation  of  the  disalicyl  aldehydes.  f/hether  this  is  entire- 
ly true  in  the  formation  of  the  dioxans  from  substituted  saligenins 
and  substituted  henzaldehydes  must  be  proven  by  further  experiment- 
al work.  The  behavior  of  nitro-saligenin  would  lead  to  the  con- 
clusion that  the  analogy  was  very  close. 


W1 


..  jfcf,'  l 

: , Qfrti  -tfe;; 


- 


- 18 


PART  IV. 

EXPERIMENTAL  PART. 

Preparation  of  disalicyl  aldehydes (4, 5-8 ,9-dibenzo-l ,3,7- 
bis-dioxan) . - Thirty  grams  (1  mole)  of  salicyl  aldehyde  and 
35  g.  (1  mole)  of  acetic  anhydride  are  mixed  and  cooled  to  0° 
in  an  ice  and  salt  mixture.  One  drop  of  concentrated  sulfuric 
acid  is  added  and  the  mixture  immediately  stirred  to  male  it  homo- 
genous. Within  ten  seconds  a deep  cherry-red  color  has  developed 
and  a vigorous  reaction  takes  place  and  is  complete  within  two  or 
three  minutes,  after  which  time  the  mixture  practically  solidifies. 
The  mass  is  stirred  thoroughly  in  order  to  be  sure  that  all  of  the 
salicyl  aldehyde  has  reacted,  and  it  is  best  to  allow  the  mixture 
to  stand  in  the  ice  for  five  or  ten  minutes  longer.  By  suction 
filtration  and  washing  with  water,  then  drying,  34  g.  of  disalicyl 
aldehyde  is  obtained  which  corresponds  to  over  85%  of  the  theory. 
There  is  even  a small  amount  more  of  product  formed  by  allowing 
the  filtrate  from  the  crystals  to  stand  for  ten  to  fifteen  minutes 
longer  in  ice. 

The  product  is  best  purified  by  recrystallization  from  alcohol 
from  which  it  forms  white,  prismatic  needles  melting  at  130°(Corr. ) 
The  melting  points  previously  reported  in  the  literature  vary  from 
137°  to  130°. 

If  a larger  amount  of  acetic  anhydride  is  used,  the  reaction 
takes  place  in  essentially  the  same  way  but  not  so  good  a yield 
results.  It  is  also  necessary  to  take  certain  precautions  in  using 
larger  amounts  of  acetic  anhydride:  the  mixture  should  not  be 


. 

- . 

• 

. 

■ 

. 

- 19  - 


allowed  to  stand  too  long  before  filtering  the  disalicyl  aldehyde 
since  the  latter  reacts  with  acetic  anhydride  in  the  presence  of 
acid  to  form  salicyl  triacetate.  With  the  smaller  amount  of 
acetic  anhydride,  the  product  precipitates  out  so  quickly  that 
there  is  no  need  for  longer  standing. 

If  the  reaction  mixture  is  not  very  carefully  controlled  in 
an  ice  and  salt  bath,  the  heat  evolved  is  so  great  that  the  mix- 
ture will  boil,  and  on  cooling,  a poorer  yield  of  disalicyl  alde- 
hyde is  obtained. 

In  place  of  concentrated  sulfuric  acid  a drop  of  glacial 
phosphoric  acid  may  be  used.  Hydrochloric  acid  is  also  a catalyst 
but  it  is  necessary  to  alter  the  procedure  slightly.  One-half  of 
the  acetic  anhydride  is  saturated  with  dry  hydrochloric  gas.  This 
saturated  solution  is  then  added  to  the  mixture  of  salicyl  alde- 
hyde and  the  other  half  of  acetic  anhydride  at  room  temperature. 

The  reaction  develops  heat  but  not  so  much  as  in  the  case  of  the 
other  acids.  A somewhat  longer  time  is  required  for  the  precipita- 
tion of  the  disalicyl  aldehyde  and  the  yields  are  not  quite  so 
high. 

Trichloroacetic  acid  may  also  be  used  as  a catalyst  but  the 
results  are  still  poorer  than  in  the  cases  already  mentioned. 

Conversion  of  disalicyl  aldehyde  to  salicyl  aldehyde  triacetate — 
Five  grams  (l  mole)  of  disalicyl  aldehyde  is  dissolved  in  14  g. 

(6  moles)  of  acetic  anhydride  and  one  drop  of  concentrated  sulfuric 
acid  is  added.  This  mixture  is  allowed  to  stand  at  room  temper- 
ature for  a day  or  two.  The  triacetate  of  salicyl  aldehyde  separ- 


. 


t 

. 

. 

. 

« 

. ' 

. . 

. 

. 

. 

- 30  - 


ates  in  large,  heavy  crystals  of  rhombic  form,  some  of  which  are 

one-fourth  to  one-half  an  inch  on  a side.  They  melt  at  100-101° 

and  do  not  lower  the  melting  point  of  salicyl  aldehyde  triacetate 

(31) 

(M. P.  100-101°)  prepared  according  to  the  method  of  Barbier. 

Preparation  of  5 , 6-Benzo-3 -phenyl -1 ,3-dioxan  (phenyl  methylene 
saligenin) . - Ten  grams  (l.l  mole)  of  saligenin  and  10  g.  (l  mole) 
of  benzaldehyde  which  has  previously  been  saturated  with  benzoic 
acid  are  heated  for  two  hours  on  a steam  cone.  A light  yellow 
resinous-looking  product  results.  The  reaction  mixture,  after 
standing  at  room  temperature  for  two  hours, is  treated  with  300  cc. 
of  a 5%  sodium  hydroxide  solution  and  cooled  in  Ice  so  that  the 
product  will  solidify.  The  white  solid  is  filtered  and  washed 
with  water.  It  is  crude  5, 6 -benzo -3 -phenyl -1 ,3-dioxan  and  corres- 
ponds to  practically  a quantitative  yield  of  product.  It  is  best 
purified  by  dissolving  3 g.  in  70  cc.  of  95%  alcohol,  adding  30  cc. 
of  water,  warming  until  a clear  solution  results  and  then  allowing 
to  stand  in  an  open  beaker  at  room  temperature.  Within  half  an 
hour  a white  crystalline  precipitate  forms.  After  two  crystal- 
lizations the  pure  material  is  produced,  melting  at  54°. 

A drop  of  concentrated  hydrochloric  acid  may  be  used  as  a 
catalyst  in  place  of  the  benzoic  acid.  It  is  then  merely  necessary 
to  heat  the  reaction  mixture  of  saligenin,  benzaldehyde  and  a 


drop  of  hydrochloric  acid  until  solution  takes  place.  The  mixture 
is  allowed  to  stand  several  hours  at  room  temperature.  The  product 
is  isolated  in  the  same  manner  as  described  above  but  the  yields 


. 


< 

. 


.. 


. 


- 21 


are  not  so  good  as  with  the  benzoic  acid  method.  If  the  reaction 
mixture,  using  hydrochloric  acid,  is  heated  longer,  the  yields  are 
in  general  still  poorer,  due  probably  to  a partial  resinif icat ion 
of  the  saligenin. 

Subs.  - 0.1343  g:  C02,  0.3885  g. : H20,  0.0715  g. 

Subs.  - 0.5957  g.  : 0.4810g.  : C6H6  43.9  g.  43.9  g.  ATF©  0.319° 
0.357° 

Calc,  for  C14H1S02:  C, 79. 3.4:  H,  5.66:  mol.  wt.  212. 

Found:  C.  78.97:  H,  5.93:  Mol.  wt.  312,313. 

5, 6-Benzo-3 -phenyl -1 ,3-dioxan  is  soluble  in  all  the  common 
organic  solvents.  It  does  not  dissolve  in  alkali  and  is  unchanged 
even  after  long  boiling  with  20%  sodium  hydroxide  solution.  When 
treated  with  concentrated  sulfuric  acid  an  immediate  decomposition 
takes  place  with  the  formation  of  benzaldehyde  and  red  lumps  of 
resinified  saligenin.  The  product  gives  no  aldehyde  or  ketone 
test  with  sodium  bisulfite,  phenyl  hydrazine  or  hydroxyl  amine: 
it  gives  no  test  with  hydroxyl  group  reagents  such  as  ferric  chlor- 
ide  or  acetic  anhydride  even  after  long  boiling.  | 

Conversion  of  5, 6-benzo-3-phenyl-l ,3-dioxan  to  benzyl i dine  di- 
acetate and  saligenin  resin.  - Ten  grams  (l  mole)  of  5,6-benzo-3- 
phenyl-l,3-dioxan  are  mixed  with  30  g.  (6  moles)  of  aoetic  anhydride 
and  one  drop  of  concentrated  sulfuric  acid  at  room  temperature. 

The  mixture  is  then  allowed  to  stand  for  several  days.  At  the  end 
of  this  time  the  acetic  anhydride  is  distilled  off  in  vacuo. 


- 33 


the  residue  taken  up  in  ether,  washed  with  water  and  then  with 
dilute  sodium  carbonate  solution.  The  ether  solution  is  then 
dried  over  anhydrous  sodium  sulfate,  the  ether  distilled,  then 
the  residue  distilled  in  vacuo.  A constant  boiling,  colorless 
fraction  comes  over  at  135°  at  4 mm.  pressure  which  on  cooling 
and  inoculating  with  a crystal  of  benzylidene  diacetata  almost 
completely  solidifies.  The  melting  point  is  45°  which  agrees  with 
that  found  in  the  literature  for  benzylidene  diacetate.  The 
residue  in  the  distilling  flask  consists  of  a light  yellow,  heavy 
oil  which  does  not  distill  at  350°  at  4 mm.  pressure,  and  at  or- 
dinary temperatures  forms  a resinous-like  mass  which  is  without 
question  a saligenin  resin. 

Preparation  of  5.6-Benzo-3-p-chlorophenyl-l , 3-dioxan  (p-chloro- 
phenyl  methylene  saligenin. ) - Two  grams  (1  mole)  of  saligenin 

and  3.35  grams  (l  mole)of  .p-ehlorobenzaldehyde  are  heated  on  a 
steam  Cone  until  all  has  dissolved  to  a clear  liquid.  This  re- 
action mixture  is  allowed  to  stand  at  room  temperature  for  two 
or  three  hours,  when  the  entire  mass  solidifies.  It  is  then 
treated  by  shaking  thoroughly  with  100  cc.  of  a 10%  sodium  car- 
bonate solution  and  filtered  by  suction.  The  whits  solid  reaction 
product  is  dissolved  in  100  cc.  of  hot  95%  ethyl  alcohol:  water  is 
added  until  the  solution  becomes  murky:  the  solution  heated  until 
clear  and  allowed  to  stand.  Within  fifteen  minutes  a heavy  white 
precipitate  forms.  This  is  the  crude  dioxan  and  corresponds  to  a 
quantitative  yield  of  the  product.  The  dioxan  is  purified  by 


- 23 


several  recrystallizations  from  alcohol  - each  time  dissolving  the 
white  solid  in  a slight  excess  of  hot  95$  ethyl  alcohol,  adding 
water  until  solution  is  murky,  heating  until  clear  and  allowing  | 
to  stand  in  an  open  beaker.  On  the  seconcL:recrystallization, 
the  product  forms  in  beautiful,  colorless  needles,  about  one-fourth 
inch  in  length  and  melting  at  107°-107.5°  (oorr. ) 

Analysis : 

Substance:  0.1303  g. : C02  - 0.3247  g. : H20, -0.00577  g. 

Calc,  for  C^HnOaCl:  C - 68.15:  H - 4.46. 

Found:  C -67.96:  H - 4.  43. 

5, 6-benzo-2-p.-*chlorophenyl-l,3-dioxan  is  soluble  in  all  the 
common  organic  solvents.  It  does  not  dissolve  in  alkali,  and  is 
extremely  stable  to  alkali.  Concentrated  sulfuric  acid  decomposes 
it  immediately  giving  the  red  resin  of  saligenin  and  p-chlorobenz- 
aldehyde. 

The  dioxan  gives  no  aldehyde  or  ketone  test  with  sodium  bi- 
sulfite, phenyl  hydrazine  or  hydroxyl  amine:  it  gives  no  test 

with  hydroxyl  group  reagents  such  as  ferric  chloride  or  acetic 
anhydride  even  after  long  boiling. 

Preparation  of  5,6-benzo-3-p-bromophenvl-l .3-dioxan  fn-bromophenvl 
methylens  saligenin).  - Two  grams  (l  mole)  of  saligenin  and  3 grams 

( 1 mole)  of  p-bromobenzaldehyde  are  heated  together  on  a steam 
cone  until  all  has  dissolved  to  a clear  solution.  This  reaction 
mixture  is  allowed  to  stand  at  room  temperature  for  eight  or  ten 
hours,  when  the  entire  mass  solidifies.  The  solid  mass  is  broken 


- 24  - 


up  and  treated  with  100  cc.  of  a 10fo  sodium  carbonate  solution 
and  filtered  by  suction.  The  white  solid  is  dissolved  in  100  cc. 
of  hot  95 $ sthyl  alcohol,  water  is  added  until  the  solution  be- 
comes murky,  and  it  is  then  heated  until  clear.  On  standing  in 
an  open  beaker,  a heavy  white  precipitate  forms  within  a half 
hour.  This  is  the  crude  dioxan  and  corresponds  to  a quantitative 
yield  of  the  product.  It  is  purified  by  several  recrystallizations 
from  ethyl  alcohol,  each  time  dissolving  the  white  solid  in  a 
slight  excess  of  hot  95$  ethyl  alcohol,  adding  water  until  solu- 
tion is  murky,  heating  until  clear  and  allowing  to  stand  in  an 
open  beaker.  On  the  second  recrystallization,  the  dioxan  forms 
in  beautiful, colorless  needles  of  varying  length  up  to  one-half 
inch  and  melting  at  117°-117.5°  (corr. ) 

This  dioxan  as  well  as  the  chlor  substituted  one  can  also  be 
condensed  in  benzene  as  a solvent.  Similar  amounts  of  saligenin 
and  aldehyde  are  dissolved  in  35  cc.  benzene  and  the  solution  re- 
fluxed for  fourteen  hours.  The  benzene  is  then  distilled  off 
and  the  sticky  white  solid  is  taken  up  in  and  recrystallized  from 
ethyl  alcohol  in  the  same  manner  as  described  above.  The  yields 
are  not  so  good  - the  best  obtainable  being  about  75$  of  theory. 

Analysis : 

Substance:  0.1183  g. : C02,  0.3507  g. : Hs0,  0.004355  g. 

Calc,  for  C^H^OsBr:  C - 57.73:  H-3.78 

Found:  C,~57.79:  H-3.68 


-35- 

5,6-benzo-3-p.-bromophenyl-l,3-dioxan  possesses  properties 
exactly  similar  to  those  of  5,6-benzo-3-p-chlorophenyl-l ,3-dioxan. 

Preparation  of  5 , 6-benzo-3-m-nltrophenyl-l ,3-dioxan  (m-nitro- 
phenyl  methylene  saligenin).  - Two  grams  (l  mole)  of  saligenin 
and  2.4  grams  (l  mole)  of  m-nitrobenzaldehyde  are  heated  together 
on  a steam  cone  for  two  hours  in  the  presence  of  a small  amount 
of  benzoic  acid  as  a condensing  agent.  The  reaction  mixture  is 
allowed  to  stand  at  room  temperature  for  a day.  A heavy  oil 
is  obtained.  This  oil  is  treated  with  100  cc.  of  a 10$  sodium 
carbonate  solution,  and  is  then  dissolved  in  50v  cc.  of  hot 
95$  ethyl  alcohol.  Just  enough  water  is  added  to  produce  slight 
murkiness:  the  solution  heated  until  clear  and  allowed  to  cool 

in  an  open  beaker.  After  an  hour  a flucculent  precipitate  will 
form.  If  an  oil  should  appear  in  this  solution  while  it  is  hot, 
it  will  solidify  on  cooling.  When  dry,  the  dioxan  has  a yellowish 
tinge.  The  yield  is  never  better  than  50$  of  theory.  The  dioxan 
can  be  recrystallized  from  ethyl  alcohol  in  a similar  manner  to 
the  other  dioxans,  but  no  definite  crystalline  structure  can  be 
obtained.  A light  flocculent  product  is  always  obtained  which 
melts  at  86°-89.5°  (corr.) 

Analysis : 

Substance:  0.1815  g. : N gas  - 15.45  cc.  (corr.) 

Calc,  for  C14Hai04N:  N - 5.447 $ 

Found:  N - 5.33$ 


- 36 


5, 6-benzo-3-m-nitrophenyl-l ,3-dioxan  possesses  properties 
exactly  similar  to  those  of  the  other  dioxans  prepared. 

Preparation  of  Saligenin  (o-hydroxy  benzyl  alcohol). 

The  saligenin  used  in  the  preparation  of  the  dioxans  is  prepared 

(33) 

according  to  the  method  of  Heckel.  This  method  involves  the 
reduction  of  salicyl  aldehyde  by  hydrogen  gas,  platinum  black 
having  been  used  as  a catalyzer  and  the  reduction  carried  out  in 
alcohol  as  a solvent.  Two  parts  (60  cc. ) of  ethyl  alcohol  and 
one  part  (30  cc. ) of  salicyl  aldehyde  are  placed  in  the  container 
of  a shaking  machine,  and  one  gram  of  platinum  black  is  added. 

The  hydrogen  is  led  in  under  pressure  in  order  to  determine  the 
amount  absorbed.  The  reduction  goes  quantitatively.  The  alcohol 
is  distilled  off  in  vacuo  and  the  saligenin  crystallized  from  hot 
benzene. 

Heckel  prepared  the  platinum  black  by  the  method  of  Will*- 
(33) 

statter.  , i.e. , by  the  reduction  of  chlor-platinic  acid  with 
formaldehyde  in  the  presence  of  alkali  in  the  cold.  If  the 
calculated  amount  of  chlor-platinic  aoid  to  give  one  gram  of 
platinum  black  is  added  to  4-6  grams  of  sodium  nitrate,  and  the 
mass  fused,  a platinum  black  is  obtained,  by  washing  away  the 
soluble  salts,  which  causes  the  reduction  of  salicyl  aldehyde 
to  saligenin  to  go  10-13  times  as  fast  as  when  Willstatters  plat- 
inum black  is  used.  This  method  for  the  preparation  of  platinum 
black  given  above  was  suggested  by  Hr.  Vorhees  in  this  laboratory. 


e 


' 


. 


* * t 


. « 


- 37  - 


Preparation  of  nitro-saligenin  (3-nitro-6-hydroxy  benzyl  alcohol) 

Nitro-saligenin  is  prepared  by  several  methods.  Hart  and  Hirsch- 
(30) 

felder,  give  a foot-note  to  their  article  on  the  preparation  of 

p-hydroxy-m-nitrophenyl  carbinol,  in  which  they  suggest  that 

nitro-saligenin  may  be  prepared  in  a similar  manner  to  the  above 

carbinol,  i.e. , by  the  action  of  bromomethyl  alcohol  on  p-nitro- 

phenol  in  the  presence  of  a small  amount  of  fused  zinc  chloride. 
(34) 

Fishman  prepares  the  3-nitro-4-hydroxy-benzyl  alcohol  by  the 

action  of  formaldehyde  on  o-nitrophenol  in  the  presence  of  a 

large  amount  of  concentrated  hydrochloric  acid.  When  p-nitrophenol 

is  used  instead  of  o-nitrophenol,  nitro  saligenin  should  result. 

The  method  was  found  to  give  very  poor  yields. 

(35) 

Einhorn,  Bischkopff  and  SzelinskJ.,  prepare  nitro-saligenin 

by  treating  m-nitro-o-oxybenzyl  amine  with  nitrous  acid. 

„ (36) 

Eichengrun,  prepares  it  by  the  action  of  chlormethyl 

alcohol  on  p-nitrophenol.  This  is  of  course,  similar  to  the 

(30) 

method  suggested  by  Hart  and  Hirschf elder. 

Nitro-saligenin  is  prepared  according  to  the  method  of  Hart 
and  Hirschf elder  as  follows: 

30  grams  of  pure  p-nitrophenol  are  mixed  in  the  cold  with 
35  grams  (an  excess)  of  bromomethyl  alcohol  and  5 grams  of  powder- 
ed fused  zinc  chloride  are  added.  The  mixture  is  kept  cold  for 
twelve  hours  and  then  allowed  to  run  at  room  temperature  for 
several  days.  The  p-nitrophenol  first  dissolves  in  the  bromo- 
methyl alcohol  and  then  the  entire  mass  solidifies.  One  liter 


, 


’ 


• • >c  ; • 


* 


' 


- 


• * 


. 


. 


• . . ; . t . BbT'  I 


. 


- 28  - 


of  water  is  added  and  the  mixture  steam  distilled  to  remove  any 

unchanged  p-nitrophenol.  The  steam  distillation  is  carried  on 

for  four  hours,  at  the  end  of  which  time,  the  liquid  remaining 
distilling 

in  the /flask  is  poured  into  a beaker,  and  allowed  to  cool.  An 
oil  separates  which  solidifies  on  further  cooling  into  colorless 
needles,  of  nitro-saligenin.  A gummy  tar  remains  in  the  distill- 
ing flask  as  a by-product.  The  nitro-saligenin  is  recrystallized 
from  hot  water  and  forms  in  almost  colorless  crystalline  needles. 
The  yield  is  about  32$  of  theory.  The  product  was  recrystallized 
several  times  from  hot  water.  The  purest  product  obtained, 
melted  at  135°-136° (corr. ) The  melting  point  recorded  in  the 
literature  is  126°.  This  melting  point  is  regarded  as  erroneous 
in  the  light  of  the  present  work,  and  the  correct  melting  point 
for  nitro-saligenin  is  given  as  136°. 

Preparation  of  bromomethyl  alcohol  - BrCHaQH . 

Bromomethyl  alcohol  is  prepared  according  to  the  method  of 

(37) 

Henry,  by  treating  formaldehyde  with  hydrogen  bromide  in  the 
cold.  The  hydrogen  bromide  is  prepared  by  passing  a mixture  of 
hydrogen  and  bromine  vapors  over  heated  platinum,  and  the  entire 
preparation  of  hydrobromic  acid  gas  and  bromomethyl  alcohol  can 
be  carried  out  in  one  continuous  apparatus  set  up.  Hydrogen 
from  a tank  is  bubbled  thru  concentrated  sulfuric  acid  and  then 
thru  dry  bromine.  The  bromine  vaporizes  sufficiently  at  room 
temperature  and  the  mixture  of  hydrogen  and  bromine  vapors  is 


- 29  - 


passed  into  a combustion  tube  containing  a spiral  of  platinum 
wire  heated  to  a dull  red.  The  catalytic  union  of  hydrogen  and 
bromine  to  form  hydrobromi.c..  acid  gas  goes  quantitatively,  based 
on  the  bromine  present.  The  hydrogen  should  be  passed  in  at 
such  a rate  as  to  insure  an  excess  of  it  over  the  bromine. 

The  hydrogen  bromide  is  then  led  through  a trap  cooled  in 
ice  to  collect  any  unchanged  bromine  and  also  to  cool  the  gas. 

It  is  then  passed  directly  into  a 40 $ solution  of  formaldehyde 
cooled  in  a freezing  mixture  of  ice  and  salt.  135  cc.  of  40$ 
formaldehyde  are  treated  with  approximately  370  grams  of  hydrogen 
bromide  in  the  course  of  seven  hours.  After  some  time,  a heavy 
red  liquid  begins  to  separate.  This  is  essentially  bromomethyl 
alcohol  and  is  formed  in  an  amount  corresponding  to  an  85$  yield. 
When  the  required  amount  of  hydrogen  bromide  has  been  passed  into 
the  formaldehyde  solution  (ascertained  by  the  fact  that  no  more 
hydrogen  bromide  is  absorbed),  the  alcohol  is  quickly  separated 
from  the  supernatent  aqueous  HBr  by  means  of  a separatory  funnel. 
The  bromomethyl  alcohol  is  kept  in  a tightly  stoppered  bottle  in 
the  cold,  as  it  decomposes  at  30°  or  more. 


. 


. 


. 


- 30  - 


PART  V 
SUMARY. 

1.  Disalicyl  aldehyde  has  been  shown  to  have  the  following 
formula: 


and  may  be  called  4,5-8,9-dibenzo-l,3,7-bis-dioxan.  It  accounts 
for  all  of  the  known  properties  of  this  substance. 

3.  A possible  mechanism  for  the  formation  of  such  a structure 
from  salicyl  aldehyde  is  given  and  from  this  mechanism  conclusions 
have  been  drawn  as  to  new  methods  by  which  it  should  be  possible 
to  prepare  disalicyl  aldehyde  from  salicyl'  aldehyde. 

3.  Disalicyl  aldehyde  may  be  formed  almost  quantitatively 
by  the  action  of  a drop  of  mineral  acid  upon  a solution  of  salicyl 
aldehyde  in  acetic  anhydride. 

4.  The  disalicyl  aldehyde  may  be  decomposed  in  the  presence 
of  an  excess  of  acetic  anhydride  by  a drop  of  mineral  acid  to 
form  salicyl  triacetate. 

5.  The  suggestion  is  made  and  proof  outlined  whereby  it  should 
be  possible  to  show  that  the  so-called  dialdan  - the  product  re- 
sulting from  two  molecules  of  aldol  with  a molecule  of  water  elim- 
inated - is  really  a bis-dioxan  with  a structure  and  properties 
very  similar  to  disalicyl  aldehyde: 


hi 

1 

H -C 


N~€  — 

I 

C«3 


- 3l  - 


c — o 

‘V  7 

o 


CH. 


c- 


5 

o 


X 


w 


<&- 

0 

M 


and  which  may  be  called  4, 8, dimethyl-1 ,3, 7-bis-dioxan. 

6.  It  was  concluded  from  the  mechanism  of  the  formation  of 
disalicyl  aldehyde  that  a compound  should  form  from  saligenin  and 
benzaldehyde  which  should  possess  similar  properties  to  disalicyl 
aldehyde.  This  substance  does  form  and  may  be  looked  upon  as 
5, 6-benzo-3 -phenyl -1 ,3-dioxan,  or  phenyl  methylene  saligenin, 
forming  white  plates  with  a melting  point  of  54°  and  having  the 
structure : 


h. 


X\/c\ 


0 

1 

c — 


W Vi 


7.  It  was  concluded  from  the  ease  with  which  5,6-benzo- 
2 -phenyl -1 ,3-dioxan  was  prepared  that  other  1,3  dioxans  could  be 
prepared  from  saligenin  and  substituted  benzaldehyde3  with  the 
result  that  the  following  1,3  dioxans  were  prepared: 

5, 6-benzo-3-p-rChlorophenyl^l ,3-dioxan,  forming  in  colorless 
needles;  melting  at  107°-107. 50° , and  having  the  structure; 


/\A" 


- 33 


5, 6-benzo-3-p-bromophenyl-l ,3-dioxan,  forming  in  colorless 


needles. 


melting  at  117°-117.5°,  and  having  the  structure: 


5 , 6-benzo-3-m-nitrophenyl-l , 3-dioxan, 
crystalline  form:  and  melting  at  88°-89.5 
structure : 


having  no  definite 
°,  and  having  the 


8.  New  information  regarding  the  preparation  of  saligenin 
is  given,  and  details  for  the  preparation  of  bromomethyl  alcohol 
and  nitro-saligenin  are  given. 

9.  The  melting  point  of  nitro-saligenin  given  in  the  liter- 
ature an  136°  was  found  to  be  erroneous,  and  136°  is  shown  to  be 
the  correct  melting  point. 


■ 


. 

, . 

. 


- 33  - 


BIBLIOGRAPHY. 

1.  Bradley,  Ber.  23,  1134  (1889) 

3.  Ettling,  Ann.  53,  77  (1845) 

3.  Cahours,  Ann.  7J3,  328  (1851) 

4.  Perkin,  Ann.  145,  399  (1868) 

5.  Zwenger,  Ann.  Spl.  J5,  43  (1870) 

6.  Gatterman,  Ann.  344,  46  (1888) 

7.  Einhorn,  Ber.  38.  3830  (1905) 

8.  Adams,  J.  Am.  Chem.  Soc.  37 , 2719  (1915) 

9.  Bradley,  Ber  23,  1134  (1889):  Am.  Chem.  J.  14,  393  (1893): 

Dains,  A zn.  Chem.  J.  16,  634  (1894). 

10.  Meyer  and  Jacobson  - Lehrbuch  der  organischen  chemie. 

Vol.  3,  Pt.  3,  Ab't.  3,  pp.  1145-1149. 

11.  Henry,  Cent.  Bl't.  1903  II  - 939. 

12.  Borsche  and  Berkhout,  Ann.  330,  83-107  (1904). 

13.  Read,  J.  of  the  Chem.  Soc.  101 , II,  2090  (1913). 

14.  Previous  references  and  also  Rivals,  Compt.  rend.  134, 

368  (1897). 

15.  Russanow,  Ber.  32.,  1944  (1889).  Michael,  Am.  Chem.  J.  £,130(1886 

16.  Olaisen,  Ann.  337 , 369  (1887). 

17.  Wurtz,  Bull.  Soc.  Chim.  28,  169  (1877). 

18.  Wurtz,  Liebigs  Jahresbericht  1873,  448. 

19.  Wurtz,  Liebigs  Jahresbericht  1876,  484. 

30.  Hart  and  Hirschf elder , J.  Am.  Chem.  Soc.  43,  II,  2683  (1930) 


f 


- 34  - 

31.  Barbier,  Bull.  soc.  chim. (3)  33,  53  (1880). 

33.  Heckel,nThe  Synthesis  of  Saligenin,"  University  of  Illinois 
Thesis,  1931. 

33.  Willstatter,  Ber.  54,  113  (1931). 

34.  Fishman,  J.  Am.  Chem.  Soc.  43,  II,  3388  (1930) 

35.  Einhorn,  Bischkopff  and  Szelinski,  Ann.  343 , 343  (1905). 

36.  Eichengrun,  Verh.  d.  Vers.  Deutsch.  Ntf.  u.  Arzte,  1901  -II, 

140:  Chem.  Centr.  1903  - II,  894. 

37.  Henry,  Ber.  37  R,  336  (1894):  Bull.  acad.  roymed.  Belg. 

(3),  36,  615. 


U|i*i*VERSrrY  0F  ,LL'NOIS-URBANA 


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